Rationale. The role of complementary and alternative interventions for prostate cancer prevention, and as an adjunct to treatment, is of great interest to the public and patients, but a highly contentious area among physicians and scientists. Soy is hypothesized, but not proven, to reduce the risk of prostate cancer or enhance the efficacy of therapy. One of the obstacles to soy consumption is the lack of consumer friendly, food-based, "phytochemical delivery systems". Our team of investigators have formulated two such systems: (a) a soy bread providing 33 mg isoflavones per 50g slice, and (b) 2-glucosidase-enriched soy bread that increases by 100% the aglycone form (potentially most active and more readily absorbed). Hypothesis. We hypothesize 2 -glucosidase-enriched soy bread will serve as an excellent source of bioavailable soy isoflavones for future phase II/III randomized clinical trials. Experimental Approach. We propose a randomized phase II cross-over trial in 40 men with prostate cancer and experiencing asymptomatic biochemical failure (rising PSA). Men will be randomized to consume 3 slices/day of soy bread or 2-glucosidase-enriched soy bread for 8 weeks and after a two week soy-free period cross over to the other arm for another 8 weeks. The following aims will be addressed. Aim 1. We hypothesize men will achieve excellent compliance with consumption of the soy breads with minimal toxicity. Aim 2. We hypothesize that consumption of the 2-glucosidase-enriched soy bread compared to control soy bread will result in an increase in the bioavailability of soy phytochemicals in the blood and provide distinct daidzein metabolite profiles. Aim 3. We hypothesize that consumption of the 2-glucosidase-enriched soy bread compared to control soy bread will have a greater effect on blood biomarkers that favor anti-cancer activity. Value: The proposed studies will characterize the ability of 2 -glucosidase-enriched soy bread to serve as a vehicle for bioactive soy phytochemicals in future definitive randomized clinical trails. PUBLIC HEALTH RELEVANCE: The public, including cancer patients, are in need of evidence based guidelines regarding dietary and nutritional products that may prevent cancer or enhance survivorship. We have developed novel soy bread products in our effort to bring desirable soy-based foods into clinical trials and, in the future, into the marketplace. The proposed study represents a critical assessment of soy bread safety/toxicity in men with prostate cancer, a group that is ideally suited for clinical trials of complementary and alternative therapy.